Rubbert A, Combadiere C, Ostrowski M, Arthos J, Dybul M, Machado E, Cohn M A, Hoxie J A, Murphy P M, Fauci A S, Weissman D
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1576, USA.
J Immunol. 1998 Apr 15;160(8):3933-41.
Cells of the dendritic lineage are thought to be among the first cells infected after mucosal exposure to HIV. In this study, we have identified the presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry. DC effectively used CCR5 for entry of macrophage (M)-tropic isolates. CCR3, the eotaxin receptor, initially identified on eosinophils, is expressed on DC and may be used as an entry coreceptor by certain dual-tropic strains. CXCR4 was not expressed on DC, although SDF-1 induced a calcium flux and DC could be infected by T cell line (T)-tropic HIV. Our findings provide evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV. DC from individuals homozygous for a 32-bp deletion of the CCR5 gene are also infectable with M-tropic strains of HIV-1, and this infection is inhibited by stromal cell-derived factor (SDF)1, suggesting that this receptor can also be used by M-tropic HIV for entry. Delineation of the spectrum of coreceptor usage on DC may offer new approaches to interfere with the initiation and propagation of HIV infection.
树突状细胞系的细胞被认为是黏膜暴露于HIV后最早被感染的细胞之一。在本研究中，我们已确定树突状细胞（DC）上存在多种趋化因子受体，它们可能作为HIV进入的共受体发挥作用。DC有效地利用CCR5来摄取巨噬细胞（M）嗜性毒株。CCR3，即最初在嗜酸性粒细胞上发现的嗜酸性粒细胞趋化因子受体，在DC上表达，并且可能被某些双嗜性毒株用作进入共受体。尽管基质细胞衍生因子-1（SDF-1）可诱导DC产生钙流且DC可被T细胞系（T）嗜性HIV感染，但DC上不表达CXCR4。我们的研究结果为DC上存在一种非CXCR4的SDF-1受体提供了证据，该受体主要被HIV的T嗜性毒株利用。CCR5基因32bp缺失的纯合个体的DC也可被HIV-1的M嗜性毒株感染，且这种感染受到基质细胞衍生因子（SDF）1的抑制，这表明该受体也可被M嗜性HIV用于进入。描绘DC上共受体使用的范围可能会为干扰HIV感染的起始和传播提供新方法。
